Immunogenicity and safety of routine vaccines in children and adolescents with rheumatic diseases on immunosuppressive treatment — a systematic review

AbstractThe immunogenicity of vaccines in children with juvenile autoimmune rheumatic diseases (JARDs) can be reduced, there are additional safety concerns around vaccination, and there is a potential for worsening in disease activity. In this systematic review, we summarise studies that investigated the immunogenicity and safety of routine vaccines in children and adolescents with JARD on immunosuppressive treatment. We identified 37 studies investigating 2571 children and adolescents with JARD on immunosuppressive treatment and 4895 control children. Of the 56 geometric mean antibody titres measured, 19 (34%) were lower, six (11%) higher, and 31 (55%) similar; of the 39 seroprotection rates measured, 10 (26%) were lower, two (5%) higher, and 27 (69%) similar; and of the 27 seroconversion rates measured, nine (33%) were lower, two (8%) higher, and 16 (59%) similar in children with JARD on immunosuppressive treatment compared with control children. However, many of the studies were underpowered, and not designed to show non-inferiority between children with JARD and controls. Subgroup analysis for different types of immunosuppressive treatments was not feasible, as most studies did not report results by treatment. Severe adverse events were reported in 38 children (33 with juvenile idiopathic arthritis, four with systemic lupus erythematosus, and one in a healthy child); most of them were likely not related to the vaccination (e.g. elective hospitalisation or surgery). A worsening in disease activity was reported in 44 (2%) children with JARD; again, many of them were likely not related to the vaccination. There were no safety concerns with live attenuated vaccines; however, only few studies reported results for this.Conclusion: Vaccination in children with JARD on immunosuppressive treatment is safe and should be promoted, especially since these children are at increased risk for infection. The importance for the completion of vaccination schedules should be stressed. Strategies to compensate for the lower vaccine responses, which are found in approximately one-third of these children, include measuring antibody levels to determine the optimal timing for the administration of additional booster doses. What is Known: • Children with juvenile autoimmune rheumatic diseases (JARDs) are at higher risk for infections, due to their underlying disease and their immunosuppressive treatment. • In children with JARD, the immunogenicity of vaccines might be reduced, and concerns about safety or the potential for worsening in disease activity after vaccination exist. What is New: • Our systematic review shows that vaccines in children with JARDs on immunosuppressive treatment are safe and immunogenic. • There are several limitations of the currently published studies, including random timing of measuring vaccine responses and age differences between children with JARD and control groups. Many of the studies were underpowered, and not designed to show non-inferiority between children with JARD and controls.

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Favourable antibody responses to human coronaviruses in children and adolescents with autoimmune rheumatic diseases

10.1101/2021.02.15.431291 ◽

2021 ◽

Author(s):

Claire T. Deakin ◽

Georgina H. Cornish ◽

Kevin W. Ng ◽

Nikhil Faulkner ◽

William Bolland ◽

...

Keyword(s):

Children And Adolescents ◽

Rheumatic Diseases ◽

Lupus Erythematosus ◽

Immunosuppressive Treatment ◽

Immune Dysfunction ◽

Inflammatory Rheumatic Diseases ◽

Igg Antibodies ◽

Autoimmune Rheumatic Diseases ◽

Human Coronaviruses ◽

The Impact

AbstractDifferences in humoral immunity to coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), between children and adults remain unexplained and the impact of underlying immune dysfunction or suppression unknown. Here, we examined the antibody immune competence of children and adolescents with prevalent inflammatory rheumatic diseases, juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM) and juvenile systemic lupus erythematosus (JSLE), against the seasonal human coronavirus (HCoV)-OC43 that frequently infects this age group. Despite immune dysfunction and immunosuppressive treatment, JIA, JDM and JSLE patients mounted comparable or stronger responses than healthier peers, dominated by IgG antibodies to HCoV-OC43 spike, and harboured IgG antibodies that cross-reacted with SARS-CoV-2 spike. In contrast, responses to HCoV-OC43 and SARS-CoV-2 nucleoproteins exhibited delayed age-dependent class-switching and were not elevated in JIA, JDM and JSLE patients, arguing against increased exposure. Consequently, autoimmune rheumatic diseases and their treatment were associated with a favourable ratio of spike to nucleoprotein antibodies.

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Outcome measures of disease activity for rare autoimmune rheumatic diseases

British Journal of Hospital Medicine ◽

10.12968/hmed.2018.79.7.396 ◽

2018 ◽

Vol 79 (7) ◽

pp. 396-401

Author(s):

Alexis Jones ◽

Alice Cotton ◽

Jesusa Guinto ◽

James Wilton ◽

Coziana Ciurtin

Keyword(s):

Disease Activity ◽

Outcome Measures ◽

Rheumatic Diseases ◽

Autoimmune Rheumatic Diseases

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Post-natalizumab disease reactivation in multiple sclerosis: systematic review and meta-analysis

Therapeutic Advances in Neurological Disorders ◽

10.1177/1756286419837809 ◽

2019 ◽

Vol 12 ◽

pp. 175628641983780 ◽

Cited By ~ 9

Author(s):

Luca Prosperini ◽

Revere P. Kinkel ◽

Augusto A. Miravalle ◽

Pietro Iaffaldano ◽

Simone Fantaccini

Keyword(s):

Multiple Sclerosis ◽

Systematic Review ◽

Disease Activity ◽

Meta Analysis ◽

Random Effect ◽

Patient Characteristics ◽

Increased Risk ◽

Disease Reactivation ◽

Definition Of ◽

High Level

Background: Natalizumab (NTZ) is sometimes discontinued in patients with multiple sclerosis, mainly due to concerns about the risk of progressive multifocal leukoencephalopathy. However, NTZ interruption may result in recrudescence of disease activity. Objective: The objective of this study was to summarize the available evidence about NTZ discontinuation and to identify which patients will experience post-NTZ disease reactivation through meta-analysis of existing literature data. Methods: PubMed was searched for articles reporting the effects of NTZ withdrawal in adult patients (⩾18 years) with relapsing–remitting multiple sclerosis (RRMS). Definition of disease activity following NTZ discontinuation, proportion of patients who experienced post-NTZ disease reactivation, and timing to NTZ discontinuation to disease reactivation were systematically reviewed. A generic inverse variance with random effect was used to calculate the weighted effect of patients’ clinical characteristics on the risk of post-NTZ disease reactivation, defined as the occurrence of at least one relapse. Results: The original search identified 205 publications. Thirty-five articles were included in the systematic review. We found a high level of heterogeneity across studies in terms of sample size (10 to 1866 patients), baseline patient characteristics, follow up (1–24 months), outcome measures (clinical and/or radiological), and definition of post-NTZ disease reactivation or rebound. Clinical relapses were observed in 9–80% of patients and peaked at 4–7 months, whereas radiological disease activity was observed in 7–87% of patients starting at 6 weeks following NTZ discontinuation. The meta-analysis of six articles, yielding a total of 1183 patients, revealed that younger age, higher number of relapses and gadolinium-enhanced lesions before treatment start, and fewer NTZ infusions were associated with increased risk for post-NTZ disease reactivation ( p ⩽ 0.05). Conclusions: Results from the present review and meta-analysis can help to profile patients who are at greater risk of post-NTZ disease reactivation. However, potential reporting bias and variability in selected studies should be taken into account when interpreting our data.

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Systematic review and meta-analysis of the epidemiology of polyautoimmunity in Sjögren’s syndrome (secondary Sjögren’s syndrome) focusing on autoimmune rheumatic diseases

Scandinavian Journal of Rheumatology ◽

10.1080/03009742.2017.1324909 ◽

2017 ◽

Vol 47 (2) ◽

pp. 141-154 ◽

Cited By ~ 15

Author(s):

H Alani ◽

JR Henty ◽

NL Thompson ◽

E Jury ◽

C Ciurtin

Keyword(s):

Systematic Review ◽

Sjögren’S Syndrome ◽

Rheumatic Diseases ◽

Sjögren's Syndrome ◽

Meta Analysis ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Autoimmune Rheumatic Diseases ◽

Secondary Sjögren’S Syndrome ◽

Sjögren‘S Syndrome

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Hybrid immunity versus vaccine-induced immunity against SARS CoV2 in Patients with Autoimmune Rheumatic Diseases

10.1101/2021.08.26.21258418 ◽

2021 ◽

Cited By ~ 1

Author(s):

Padmanabha Shenoy ◽

Sakir Ahmed ◽

Aby Paul ◽

Somy Cherian ◽

Rashwith Umesh ◽

...

Keyword(s):

Single Dose ◽

Rheumatic Diseases ◽

Natural Infection ◽

Double Dose ◽

Immune Protection ◽

Neutralization Potential ◽

Vaccine Responses ◽

Autoimmune Rheumatic Diseases ◽

Induced Immunity ◽

Dose Vaccine

AbstractIntroductionSingle-dose COVID-19 vaccines in healthy individuals with past COVID-19 infections seem to provide better immunity than double doses in COVID-19 unexposed individuals. However, it is not known whether the same is true for patients with autoimmune rheumatic diseases (AIRD) who are on immunosuppressants.MethodsWe identified 30 patients with AIRD who took a single dose of the ChAdOx1 vaccine post-COVID-19 infection. Age, sex and disease similar patients were enrolled in to three groups of 30 each who had (1) past infection with COVID-19 but no vaccine, (2) a single dose of ChAdOx1 and (3) double doses of ChAdOx1. Sera were collected from each patient approximately 30 days after last vaccine dose or since the onset of COVID19 symptoms (in the unvaccinated group). Antibodies to spike protein were estimated and virus neutralization potential of sera was tested.ResultsBaseline characteristics including drug usage was similar betweenthe groups. Seroconversion occurred in 25(83%), 23(77%), 27(90%), and 30(100%) in natural infection, single-dose vaccine, double dose vaccine, and infection +single dose vaccine groups respectively. Mean antibody titres (10076.8±8998) in the last group were at least 6-100x higher than in the other 3 groups. Also, the infection +vaccine group had the highest neutralization potential of 83.37 % as compared to 45.4% in the fully vaccinated group.ConclusionThe hybrid immunity with a single dose of the vector-based vaccine post-infection seems to be superior to double dosage of the vaccine in patients with AIRD. A universal vaccination strategy involving a single dose of vaccine for all individuals with previous COVID-19 infection seems to be effective in these patients also.What is already known about this subject?A single dose of an RNA based COVID-19 vaccine after COVID-19 natural infection provides superior immune protection as compared to double doses of vaccines in infection naïve personsA second dose of vaccine in healthy people who had infection previously does not increase the immune protection but may paradoxically induce toleranceVaccine responses in patients with autoimmune rheumatic diseases(AIRD) may be suboptimal due to underlying disease or the use of immunosuppressants.What does this study add?Hybrid-induced immunity (single vaccine post COVID-19 infection) produces adequate vaccine responses in patients with AIRD, non-inferior to double dose of vaccineBesides mRNA vaccines, the adenoviral vector vaccine AZD1222 also demonstrates this hybrid phenomenon.How might this impact on clinical practice?Vaccination policies can consider providing only a single vaccine in those who had previous COVID-19 infection. This strategy has been shown not to be harmful for patients with AIRD. This will help reduce vaccine shortages.

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A systematic review exploring the bidirectional relationship between puberty and autoimmune rheumatic diseases

10.21203/rs.3.rs-45432/v1 ◽

2020 ◽

Author(s):

Nina M de Gruijter ◽

Meena Naja ◽

Hannah Peckham ◽

Anna Radziszewska ◽

Matthew Kinsella ◽

...

Keyword(s):

Systematic Review ◽

Rheumatic Diseases ◽

Lupus Erythematosus ◽

Meta Analysis ◽

Severe Disease ◽

Delayed Puberty ◽

Future Research ◽

Autoimmune Rheumatic Diseases ◽

Bidirectional Relationship ◽

The Impact

Abstract Background: Autoimmune rheumatic diseases (ARDs) are associated with a significant sex-bias which becomes more evident post-puberty. This systematic review aims to elucidate the bidirectional relationship between puberty and ARDs related outcomes.Methods: Studies published in English until October 2019 were identified using a systematic search of endocrinology and rheumatology literature. Information was extracted on study design, sample size, demographics, puberty outcome measures, and main findings. The methodological quality of the studies included was analysed using the Newcastle-Ottawa Scale (NOS).Results: 14 non-randomised studies reporting on the impact of puberty on ARD outcomes (n = 7), ARD impact on puberty-related outcomes (n = 6), or both (n = 1) have been identified. The impact of puberty on ARD outcomes have been investigated in patients with juvenile idiopathic arthritis (JIA)-associated uveitis (n = 1), juvenile systemic lupus erythematosus (JSLE) (n = 5) or in healthy controls who developed adult-onset SLE (n = 1) or had non-specific symptoms (n = 1). The impact of ARD on puberty outcomes was explored in JIA (n = 4) and JSLE (n = 3). Quality assessment of studies showed a small to moderate risk of bias overall (NOS 4–9/9). Due to large heterogeneity of the studies it was not possible to perform a meta-analysis. Multiple studies reported on delayed puberty in patients with JIA/JSLE, menstrual and hormonal abnormalities, and lower height and weight than controls. Earlier (pre-pubertal) onset of JSLE was correlated with more severe disease and more need for systemic treatment.Conclusion: A bidirectional relationship exists between puberty and ARDs; however, more and better research is required to elucidate the complexity of this relationship. We propose puberty-related clinical assessments in patients with ARDs, which can improve patient outcomes and facilitate future research.

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The influence of disease activity on pregnancy outcomes in women with inflammatory bowel disease: A systematic review and meta-analysis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjaa225 ◽

2020 ◽

Author(s):

Min-A Kim ◽

Young-Han Kim ◽

Jaeyoung Chun ◽

Hye Sun Lee ◽

Soo Jung Park ◽

...

Keyword(s):

Systematic Review ◽

Preterm Birth ◽

Disease Activity ◽

Spontaneous Abortion ◽

Pregnancy Outcomes ◽

Meta Analysis ◽

Cochrane Library ◽

Increased Risk ◽

Adverse Pregnancy ◽

The Impact

Abstract Background & Aims Robust evidence regarding the impact of disease activity on pregnancy outcomes in women with IBD is crucial for both clinicians and patients in preparing a birth plan. We sought to perform a systematic review and meta-analysis to assess the pooled influences of disease activity on pregnancy outcomes in women with IBD. Methods We searched MEDLINE, EMBASE, and COCHRANE library to identify articles comparing pregnancy outcomes between active and inactive IBD at the time of conception or during pregnancy. A meta-analysis was performed using a random-effects model to pool estimates and report odds ratios (ORs). Results A total of 28 studies were identified as eligible for the meta-analysis. In women with active IBD, the pooled ORs for low birth weight (LBW), preterm birth, small for gestational age (SGA), spontaneous abortion, and stillbirths were 3.81 (95% confidence interval [CI] 1.81-8.02), 2.42 (95% CI 1.74-3.35), 1.48 (95% CI 1.19-1.85), 1.87 (95% CI 1.17-3.0), and 2.27 (95% CI 1.03-5.04) compared to women with inactive IBD, respectively. In the subgroup analysis based on disease type, women with active ulcerative colitis had an increased risk of LBW, preterm birth, and spontaneous abortion. Women with active Crohn’s disease had a higher risk of preterm birth, SGA, and spontaneous abortion. Conclusions Active IBD during the periconception period and pregnancy is associated with increased risk of adverse pregnancy outcomes. Our data suggest that pregnancy should be planned when the disease is quiescent, and continuous disease control is important even during pregnancy.

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